Abstract
Host responses to Mycobacterium tuberculosis infection provide a basis for diagnosis of latent infection and active disease. T cell responses have been the mainstay for diagnosis of latent infection and may contribute to diagnosis of active disease. Recent advances in characterizing humoral responses will likely contribute to improved diagnosis of active disease. However, these measures fail to distinguish the continuum of infection states. Moving to a systems approach to biomarker discovery may provide the resolution that current methods of diagnosis lack. The chapter evaluates the current use of T cell and B cell responses for diagnosis and the limitations of applying them separately. The possibility that macrophage or monocyte activation may serve as a biomarker is also addressed. We consider whether methodologies that combine (a) multifunctional T cell responses and T cell types, (b) monocyte/macrophage characteristics that reveal response to infection, and (c) dominant B cell responses to M. tuberculosis growth-phase-specific antigens can further contribute to a systems approach for biomarker discovery that can distinguish among infection states.